Body

ORLANDO, Fla. (September 12, 2019) - Personalized medicine - where the proper medicine and proper dose are used for the individual patient - moved a step closer to reality for children suffering from eosinophilic esophagitis (EoE), an inflammation of the food pipe often caused by an allergic reaction to certain foods. The study, led by researchers from Nemours Children's Health System and published today in the Journal of Pediatric Gastroenterology & Nutrition, suggests that a simple genetic test from a saliva sample may greatly boost response rates in children with eosinophilic esophagitis who are treated with a class of medications called proton pump inhibitors (PPIs), which are commonly prescribed to treat acid-related conditions.

"Currently only 30 to 60 percent of children respond when treated with proton pump inhibitors to reduce inflammation from eosinophilic esophagitis," said senior author James P. Franciosi, MD, Chief of Gastroenterology, Hepatology and Nutrition for Nemours Children's Hospital. "Our study found that treatment response is strongly influenced by common genetic variants that affect how the body metabolizes or responds to PPIs. These findings could lead to individualized therapy based on a person's genetics."

Eosinophilic esophagitis (EoE) is a chronic immune condition that leads to inflammation of the esophagus. Symptoms include difficulty swallowing, abdominal pain, nausea, and vomiting. EoE is considered rare, but new diagnoses are increasing, along with the total number of patients. PPIs, which are often prescribed for a more common condition--gastroesophageal reflux disease, or GERD--are one treatment for EoE.

The research team analyzed DNA from esophageal tissue biopsies of 92 patients, from 2 to 16 years old. In children who received PPI therapy for EoE, the study found patients with a combination of certain common gene variants were nearly nine times more likely to fail to respond to PPI treatment. They also found that based on the genetic analysis, some patients were less likely to respond to certain dose levels, and genotyping may allow for more accurate customization of doses.

"Without considering information about a patient's genetics, clinicians may be prescribing a lower or higher PPI dose than is necessary, which could lead to treatment failure or PPI-associated side effects including upper respiratory and GI tract infections," said lead author Edward B. Mougey, PhD, of Nemours' Center for Pharmacogenomics and Translational Research. "The general strategy of dose adjustment to compensate for genetic variants of drug-metabolizing enzymes carried by an individual is the cornerstone of precision medicine."

Dr. Franciosi notes that the next step for this research is to conduct clinical trials for EoE and acid-related disorders such as GERD to determine exactly how to adjust PPI dose based on an individual's genetics. He said, "Using genetics to personalize PPI drug therapy to the individual patient may ultimately improve efficacy and reduce side effects, resulting in significant benefits for many children."

WASHINGTON--A plant-based diet may alleviate painful symptoms associated with rheumatoid arthritis (RA), according to a new review published in the journal Frontiers in Nutrition.

RA is an autoimmune disorder characterized by inflammation that causes pain and swelling. While genetic factors are important, studies show that lifestyle factors, including diet, play a role. Researchers with the Physicians Committee for Responsible Medicine reviewed clinical trials and observational studies and found strong and consistent evidence that a plant-based dietary pattern can reduce inflammation and improve symptoms associated with RA.

The study authors highlight four ways a plant-based diet may be effective:

1. Plant-based diets reduce inflammation. A 2015 study found that participants randomized to a two-month plant-based dietary intervention experienced reductions in inflammatory scores, when compared to those eating diets higher in fat and animal products. Other studies have found that diets high in fat and processed meat are associated with inflammatory markers, including C-reactive protein (CRP). Plant-based diets and high-fiber diets have been associated with lower CRP levels.

2. Plant-based diets reduce RA pain and swelling. A randomized clinical trial that looked at the effects of a low-fat vegan diet on people with moderate-to-severe RA found that after just four weeks on the diet, participants experienced significant improvements in morning stiffness, RA pain, joint tenderness, and joint swelling. The review authors suggest that plant-based diets are typically low in fat and high in fiber, which can reduce inflammation and decrease pain and swelling.

3. Plant-based diets are associated with a lower BMI. Studies show that excess body weight increases the risk for developing RA and decreases the likelihood of remission if RA is already present. A 2018 analysis found that RA patients who lost more than 5 kilograms of body weight were three times more likely to experience improvements than those who lost less than 5 kilograms. Plant-based diets have consistently proven to be effective for weight loss.

4. Plant-based diets promote healthy gut bacteria. Some studies suggest that the microbiome may play a key role in RA and inflammation. The authors note that high-fiber plant-based diets can alter the composition of gut bacteria and increase bacterial diversity, which is often lacking in RA patients.

"A plant-based diet comprised of fruits, vegetables, grains, and legumes may be tremendously helpful for those with rheumatoid arthritis," says study co-author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee. "This study offers hope that with a simple menu change, joint pain, swelling, and other painful symptoms may improve or even disappear."

While more research is needed, the review adds to the evidence that diets rich in fruits, vegetables, whole grains, and legumes may be beneficial for autoimmune conditions. Other studies have found that a plant-based diet may be protective against hypothyroidism, hyperthyroidism, and multiple sclerosis.

San Antonio, Texas (September 11, 2019) - Tuberculosis and HIV - two of the world's deadliest infectious diseases - are far worse when they occur together. Now, Texas Biomedical Research Institute researchers have pinpointed an important mechanism at work in this troubling health problem. And, their discovery could lead to a new mode of treatment for people at risk. The results were published in the Journal of Clinical Investigation, a top-tier venue for critical advances in biomedical research.

"We were a little surprised at the extent of clarity in our data," Professor and Southwest National Primate Research Center Director Deepak Kaushal, Ph.D., said. "I am actually very excited to move forward trying different treatment approaches on co-infected monkeys."

The scientific community has long assumed the reason people with HIV are more likely to develop TB is a depletion of immune cells called CD4+ T cells. However, Dr. Kaushal's team was able to show that other effects of viral co-infection play a crucial role in this process.

Using about 40 rhesus macaques, researchers determined that lung-specific chronic immune activation is responsible for the progression of disease. Chronic immune activation is a dysfunction of immune pathways that generate molecules (cytokines and chemokines) which fight off pathogens like bacteria, viruses and fungi.

Dr. Kaushal used an analogy to explain what this dysfunction caused by HIV infection does in the body. "It's like all the taps and faucets in your house are turned on full blast all the time," he said. "You are going to lose a lot of water. With this dysfunction, all cytokines ad chemokines are constantly being produced to the highest levels. This dysregulates the body's ability to fight off other infections."

Even with the gold standard antiretroviral therapy (ART) for people with HIV, chronic immune activation still persists. Dr. Kaushal said his study shows "we need to develop approaches to target chronic immune activation," perhaps with a drug that would be an additional therapy along with ART.

Dr. Kaushal said the implications of a new method of treatment are enormous. Up to a fourth of the world's population is infected with tuberculosis. Most of the time, the bacterial disease remains latent (dormant). In otherwise healthy people with latent TB, only 5% will go on to develop active tuberculosis. In HIV/AIDS patients, the risk of developing active TB increases ten-fold to 50%. TB and HIV co-infection is considered a global syndemic, meaning the diseases are pandemics infecting people all around the world, and they promote each other. In parts of Sub-Saharan Africa, the rate of TB/HIV co-infection is "astronomically high," according to Dr. Kaushal, citing statistics that show it's 100 times higher than the rest of the world.

This discovery was 12 years in the making, starting with the creation of a nonhuman primate model for TB/HIV co-infection. Dr. Kaushal said he is hopeful new treatment strategies could reach the clinic within a decade.

A person with drug resistant epilepsy who gets an early surgical intervention has a better chance of becoming seizure free. This is shown in a systematic review and meta-analysis in which Sahlgrenska Academy researchers, in collaboration with the Swedish Council for Assessment of Health Technology and Social Services (SBU), analysed results from a range of previous studies. They concluded that people with drug resistant epilepsy should, as early as possible, be referred for epilepsy surgery evaluation.

Some 65,000 people in Sweden, including 11,000 children, have epilepsy. Many are helped by the epilepsy drugs that are available. Among those who are not fully freed from attacks, a high proportion nevertheless undergo a marked improvement.

For some patients in whom the drugs do not work, who must then live with severe epileptic seizures, surgery may be efficacious - but only if the epilepsy comes from an operable region of the brain.

"Drug resistant epilepsy affects every aspect of life, and no other treatment is as effective as epilepsy surgery. Before the surgical option is chosen, an advanced investigation is needed, to show that the person's attacks come from this limited region in the brain," says Kristina Malmgren, senior professor at Sahlgrenska Academy and consultant physician at Sahlgrenska University Hospital.

Jointly with the Swedish Council for Assessment of Health Technology and Social Services (SBU), Kristina Malmgren and her colleagues have compiled a systematic literature overview and meta-analysis of studies investigating associations between early or later operations and the chances of seizure freedom. This meta-study has formed part of the basis for the national guidelines on epilepsy recently adopted by the Swedish National Board of Health and Welfare, and the results have now been published in the highly reputed journal Neurology.

Today, there is sound scientific support for the view that people with drug resistant epilepsy, compared with their prospects if they continue to receive drug treatment only, have better prospects of being seizure free, or of the frequency of attacks being greatly reduced, if they can undergo surgical treatment for their epilepsy.

"Earlier studies have shown that a lot of people who are operated on for epilepsy have had it for many years -- often half their lives. It has been shown that being operated can mitigate many of the adverse consequences of the epilepsy. There are also certain studies providing evidence that the chances of post-operative seizure freedom improve if the person undergoes the surgery at an earlier stage, compared with a later one," Malmgren says.

The meta-analysis comprises 12 studies that examined the outcomes of surgery on patients who had previously had epilepsy for between two and 20 years. The probability of being spared from attacks was 15-21 per cent higher for those who were operated on at an earlier stage. However, the authors point out that the degree of evidence for the studies included was low, since these were observation studies of only average quality.
"The duration of the epilepsy is the only known predictor of freedom from attacks following surgery for epilepsy that can be influenced. The study therefore underlines the importance of people with drug resistant epilepsy being investigated for a possible epilepsy operation as soon as possible."

Malmgren adds that it is never too late to offer epilepsy surgery, since its benefits persist even if the epilepsy has lasted many years.

"This knowledge may result in people with hard-to-treat epilepsy being referred much more often for assessment of whether epilepsy surgery is a suitable form of treatment for them," she concludes.

Decoding Messages in the Body's Microscopic Metropolises

by Aliyah Kovner

A study aimed at identifying and examining the small messenger proteins used by microbes living on and inside humans has revealed an astounding diversity of more than 4,000 families of molecules - many of which have never been described previously.

The research, led by Stanford University and now published in Cell, lays the groundwork for future investigations into how the trillions of bacteria, archaea, and fungi that compose human microbiomes compete for resources, attack and co-exist with one another, and interact with our own cells.

"Because it is much more difficult to search for sequences encoding small proteins than it is to trawl for large proteins, our comprehension of the small proteins expressed by microbial communities has always been lacking," said Nikos Kyrpides, a Berkeley Lab senior scientist who contributed to the work. Yet, very small proteins made of 50 or fewer amino acids, which can move though cell walls and membranes, perform many essential tasks that mediate an organism's interactions with the environment. These functions, combined with the fact that they are easier to synthesize and manipulate than large molecules, make small microbial proteins a potential source of new medicines.

Learn more about this study here.

X-ray Experiments Contribute to Studies of a Drug Now Approved to Combat Tuberculosis

By Glenn Roberts

The U.S. Food and Drug Administration has approved a new antibiotic that, in combination with two existing antibiotics, can tackle one of the most formidable and deadly treatment-resistant forms of the bacterium that causes tuberculosis. The new antibiotic, called pretomanid (PA-824), can work with the other drugs like a deadly cocktail - triggering the bacteria (Mycobacterium tuberculosis) to release nitric oxide. This can burst the bacteria's cell walls and poison the microorganisms.

Studies exploring the structure and function of the new drug benefited from X-ray experiments at Berkeley Lab's Advanced Light Source (ALS). ALS experiments detailed the molecular structure of Ddn, a tuberculosis bacterium enzyme, in the presence and absence of a coenzyme (F420). Coenzymes, or cofactors, can help enzymes carry out chemical reactions. SLAC National Accelerator Laboratory's Stanford Synchrotron Radiation Lightsource (SSRL) also carried out related experiments. ALS and SSRL are DOE Office of Science user facilities.

Drug-resistant strains of tuberculosis bacteria infected an estimated 558,000 people in 2017. Existing treatments are often unsuccessful and can include as many as eight antibiotics taken for 18 months or longer. The World Health Organization has reported a 55% success rate in treating multi-drug resistant tuberculosis using existing treatments.

In a Phase III clinical trial, the three-drug regimen that includes the new FDA-approved antibiotic cleared the infection within six months from 95 of 109 patients who were unresponsive to previous treatments.

Work at the ALS has also benefited research into cancer-fighting drugs, and the fight against the Ebola and Zika viruses, among other examples.

Read the FDA announcement:FDA approves new drug for treatment-resistant forms of tuberculosis that affects the lungs.

A Chemical Reaction Close-Up: New Technology Gives a Glimpse of Solar Fuel Generation in Action

By Aliyah Kovner

Electrochemical devices that use sunlight to generate fuel represent a promising means of harvesting sustainable energy; but currently, none are efficient enough for real-world applications. One of the main reasons for the slow development is the difficulty in observing and measuring what is happening at the liquid-catalyst interface - the location in the cell where the fuel-producing chemical reactions are taking place - without interfering with the processes.

Hoping to break this barrier, scientists at the Joint Center for Artificial Photosynthesis, a Department of Energy Innovation Hub based partly at Berkeley Lab, have invented a cell that is specially designed to allow for unobtrusive observation of an isolated, operating catalyst. A description of the cell is published in Physical Chemistry Chemical Physics.

"Our design can mimic how a catalyst behaves in a full device, thanks to a fast-flow design that constantly replenishes the liquid at the interface," said lead author Walter Drisdell, a Berkeley Lab chemist. "And the cell shape allows X-ray beams to graze over the surface, showing us the chemistry at the interface specifically."

The cell is expected to help scientists engineer and test new catalyst materials, which can be used in next-generation solar fuel devices that split water to produce hydrogen gas and convert carbon dioxide emissions into fuels like ethanol.

"We intend to make the cell available to users at the DOE's Stanford Synchrotron Radiation Lightsource (SSRL) facility so the entire science community can benefit from it," said Drisdell. SSRL is a DOE Office of Science user facility.

Media contact: Laurel Kellner, LKellner@lbl.gov, 510-590-8034

Scientists have determined a new way to protect the hair follicle from chemotherapy in an effort to prevent hair loss as a result of cancer treatments.

Researchers based at The University of Manchester have discovered a new strategy for how to protect hair follicles from chemotherapy, which could lead to new treatments that prevent chemotherapy-induced hair loss - arguably one of the most psychologically distressing side effects of modern cancer therapy.

The study from the laboratory of Professor Ralf Paus of the Centre for Dermatology Research describes how damage in the hair follicle caused by taxanes, cancer drugs which can cause permanent hair loss, can be prevented.

To do this, scientists have exploited the properties of a newer class of drugs called CDK4/6 inhibitors, which blocks cell division and are already medically approved as so-called "targeted" cancer therapies.

Dr Talveen Purba, lead author on the study explains: "Although at first this seems counterintuitive, we found that CDK4/6 inhibitors can be used temporarily to halt cell division without promoting additional toxic effects in the hair follicle. When we bathed organ-cultured human scalp hair follicles in CDK4/6 inhibitors, the hair follicles were much less susceptible to the damaging effects of taxanes"

Taxanes are very important anti-cancer drugs commonly used to treat, for example, patients with breast or lung carcinoma and particularly cause anxieties among breast cancer patients for the very distressing and sometimes long-lasting hair loss taxanes can induce. (Thousands of patients in the US are currently suing pharmaceutical company Sanofi over a lack of warning of the risk of permanent hair loss after treatment with the taxane drug Taxotere.)

Dr Purba emphasises: "A pivotal part of our study was to first get to grips with how exactly hair follicles responded to taxane chemotherapy, and we found that the specialised dividing cells at the base of the hair follicle that are critical for producing hair itself, and the stem cells from which they arise, are most vulnerable to taxanes. Therefore, we must protect these cells most from undesired chemotherapy effects - but so that the cancer does not profit from it."

The team hope that their work will support the development of externally applicable medicines that will slow or briefly suspend cell division in the scalp hair follicles of patients undergoing chemotherapy to mitigate against chemotherapy-induced hair damage. This could complement and enhance the efficacy of existing preventive approaches i.e. scalp cooling devices.

The researchers underscore that more work is desperately needed in this lamentably under-funded field of cancer medicine, where patients have waited for so long to see real breakthroughs in pharmacological hair loss prevention.

Dr Purba said: "Despite the fact that taxanes have been used in the clinic for decades, and have long been known to cause hair loss, we're only now scratching the surface of how they damage the human hair follicle."

He added: "We also don't really know why some patients show greater hair loss than others even though they get the same drug and drug-dose, and why it is that certain chemotherapy regimens and drug combinations have much worse outcomes than others"

"We need time to further develop approaches like this to not only prevent hair loss, but promote hair follicle regeneration in patients who have already lost their hair due to chemotherapy."

Even though exercise is known to be healthy, many people find it difficult to maintain an exercise program for a longer time. This applies even more to people with a chronic illness such as Parkinson's disease, where physical and mental limitations are additional obstacles. The Park-in-Shape study, funded by ZonMW (Netherlands Organization for Health Research & Development), tested an innovative solution for this challenge. The participants were divided into two groups. Both groups had a motivational app at their disposal, which offered the participants rewards for exercising. The control group only performed stretching exercises, while the active intervention group was instructed to exercise for 30-45 minutes on a stationary bicycle at home, at least three times a week.

The active group's exercise bikes were also equipped with motivating games, making the program more entertaining and challenging for the participants. For example, the participants could race against their own previous performance - a "ghost rider" - or against a group of other cyclists. The system adjusted the difficulty of the game to the patient's heartbeat, making the challenge just right. The challenges also became more difficult as the participants got fitter.

Thanks to these motivating elements, the participants faithfully complied with the cycling exercise regime three times a week for 6 months. After the study, the cycling patients had a significantly better cardiovascular fitness, which has many obvious advantages. The motor disability of the cycling group was also significantly better: according to the gold standard (the MDS-UPDRS score), the cycling group scored on average 4.2 points lower than the control group. This is a rather large effect, comparable to that of several conventional Parkinson's drugs. PhD candidate Nicolien van der Kolk: "We were pleasantly surprised that people with Parkinson's disease were able to adhere to their exercise regimes so well. The beneficial effect on their motor disability was also large enough to be clinically relevant. As such, exercise is a very useful addition to the medication."

The fact that this cycling exercise can take place entirely at home is a major advantage for patients, as this greatly enhances the feasibility of the treatment. Principal investigator Professor Bas Bloem: "This study is very important. We can now start researching whether much more long-term cycling can also slow the disease progression. Also, this new 'exergaming' approach that we have developed is very suitable to achieve long-term improvements in exercise behavior for patients with a range of other disorders that could also benefit from regular exercise."

Cefas and University of Exeter scientists have presented a novel concept describing the complex microbial interactions that lead to disease in plants, animals and humans.

Microbial organisms and viruses cause many diseases of plants and animals.

They can also help protect from disease, for example the complex communities of microbes in the human gut, which are very important for our health.

However, very little is known about these microbes and how they cause and prevent disease.

The pathobiome concept opens a door on this unexplored world of microbial diversity and how it controls all other organisms on the planet.

It will change the way we approach health and disease control in animals, plants and humans.

Traditional approaches to describe infectious disease in plants, animals and in humans are based on the concept that single pathogens are responsible for the signs or symptoms of disease observed in those hosts.

The pathobiome concept explains that in reality, disease occurrence is much more complex.

Today sees the publication of a paper exploring the pathobiome concept, a novel way of seeking to understand diseases of plants and animals, including humans.

The concept acknowledges that all organisms are in fact complex communities of viruses, microbes and other small organisms (e.g. parasites) which can interact to affect health or disease status at any given time.

These complex communities continually interact with their hosts, sometimes conferring benefits (e.g. "good" bacteria in the human gut microbiome), and at other times causing harm by contributing to disease.

When these communities combine to cause disease they are termed "pathobiomes" - a recognition of their collective shift away from the healthy-state "symbiome".

The recognition that the pathobiome plays a key role in those signs and symptoms of disease that we observe in the host is becoming a more accurate way of considering disease than by simply referring to it as the outcome of the effects of a single pathogen (e.g. the influenza virus).

Even when a single agent is implicated, its effects are likely to be modified (enhanced or mitigated) by others in the accompanying pathobiome and so should not be considered in isolation in the disease process.

The influence of the surrounding environment on animal and plant health is hugely important too.

For example, aquatic organisms live in a microbial soup; there are millions of microbes and viruses in every drop of fresh and seawater.

Some of these are already known to cause diseases in different organisms.

In other cases, microbes not previously thought to be pathogenic can, in fact, become so under certain environmental conditions.

As a result of this we are revising our understanding of what a pathogen actually is as we start to recognise that this can be determined by the context in which a microbe finds itself.

Professor David Bass, lead author at Cefas, said: "The vast majority of cells in our bodies are bacterial, not human.

"Therefore, we are walking ecosystems - interacting communities of many different organisms.

"This is also true for all other animals and plants.

"The organisms in these complex communities play key roles in determining the health of their host animals and plants.

"The pathobiome concept will lead to understanding these relationships better and help us manage disease in crop plants and animals, wildlife, pets and ourselves."

Professor Charles Tyler, of the University of Exeter said: "As we seek to better understand how pathogens cause diseases, we increasingly recognise that the environment, of both the host and pathogen, plays a vital role.

"The concept of the pathobiome seeks to understand how interactions between organisms in, and immediately surrounding, a host, together with the associated physicochemistries of those environments enable or inhibit an organisms' ability to cause disease.

"As such this presents a more holistic and realistic approach to understanding the disease process.

"It is great to see this conceptual paper coming out of the Centre for Sustainable Aquaculture Futures - a partnership between the University of Exeter and Cefas, where disease diagnosis, avoidance and mitigation of disease in aquaculture is a major focus."

Professor Grant Stentiford, co-author and Science Theme Lead for Animal and Human Health at Cefas said: "Conceptualising the pathobiome as a community of microbes which have the capacity to change in the host over space (e.g. between tissues and organs) and time, and are associated with observable changes in the health of the host, will revolutionise our understanding of how to describe and manage disease in animals and plants.

"In the case of farmed animals and plants, optimising those conditions which discourage formation of a pathobiome may become as important as existing controls, which aim to minimise exposure to single, specific pathogens."

PITTSBURGH--Wearable sensors such as smartwatches have become a popular motivational tool for fitness enthusiasts, but gadgets do not sense all exercises equally. Researchers at Carnegie Mellon University have found that a stationary camera is a better choice for gym exercises.

The vision-based system, called GymCam, detects repetitive motions. By doing so, Rushil Khurana and Karan Ahuja, both Ph.D. students in CMU's Human-Computer Interaction Institute (HCII), found that they could detect exercises in a gym. Moreover, they could recognize the type of exercise and reliably count repetitions.

"In a gym, the repetitive motion almost always is an exercise," said Mayank Goel, assistant professor in the HCII and Institute for Software Research. "If you are moving both your arms, you tend to move them together in time. However, if two people are exercising next to each other and performing the same exercise, they are usually not in sync, and we can tell the difference between them."

Because the system only needs motion information, the camera feed can be reduced to pixel-by-pixel changes and eliminate identifiable faces that would intrude on privacy.

Khurana said that reliance on motion information also addresses a problem for single-camera systems in a crowded gym environment -- the inability to see a person's whole body. Gym equipment or other people can often obscure the camera's view. GymCam, however, can detect exercise as long as its camera can see any body part moving repetitively.

Khurana and Ahuja will present their findings Thursday, Sept. 12, at the International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2019) in London.

Ahuja said smartwatches and other wearables do a reasonable job of tracking many cardio exercises and some strength-training exercises. But their effectiveness depends on where the wearables are worn. A smartwatch might sense a dumbbell lift, but is useless for leg presses. Moreover, it is hard for a watch to differentiate between several body motions. Instrumenting the exercise machines is an option, but an expensive one. A camera, however, is relatively cheap and provides spatial as well as motion information.

The system can also learn the location of types of exercise machines or certain exercise stations in a gym. It can then use an individual's location, in addition to their movements, to determine the exercise they're doing.

The researchers tested their algorithm in a crowded gym. But Goel said that the same algorithm works perfectly on a smartphone as well, so a person can use their phone to record and track their workouts at home. Some companies have already expressed interest in using the system for tracking in-home exercises.

The system also might have uses beyond physical exercise. Goel said the camera system, combined with smartwatches worn by individuals, might help people with visual disabilities navigate shopping malls, airports and other public spaces. Instead of using the person's face as their identity, the system will use their motion as their signature. It allows people to easily opt-out of being tracked or located.

Researchers from Charité - Universitätsmedizin Berlin and the German Cancer Consortium (DKTK) have successfully solved a longstanding problem in the diagnosis of head and neck cancers. Working alongside colleagues from Technische Universität (TU) Berlin, the researchers used artificial intelligence to develop a new classification method which identifies the primary origins of cancerous tissue based on chemical DNA changes. The potential for introduction into routine medical practice is currently being tested. Results from this research have been published in Science Translational Medicine*.

Every year, more than 17,000 people in Germany are diagnosed with head and neck cancers. These include cancers of the oral cavity, larynx and nose, but can also affect other areas of the head and neck. Some head and neck cancer patients will also develop lung cancer. "In the large majority of cases, it is impossible to determine whether these represent pulmonary metastases of the patient's head and neck cancer or a second primary cancer, i.e. primary lung cancer," explains Prof. Dr. Frederick Klauschen of Charité's Institute of Pathology, who co-led the study alongside Prof. Dr. David Capper of Charité's Department of Neuropathology. "This distinction is hugely important in the treatment of people affected by these cancers," emphasizes Prof. Klauschen, adding: "While surgery may provide a cure in patients with localized lung cancers, patients with metastatic head and neck cancers fare significantly worse in terms of survival and will require treatments such as chemoradiotherapy."

When trying to distinguish between metastases and a second primary tumor, pathologists will usually use established techniques such as analyzing the cancer's microstructure and detecting characteristic proteins in the tissue. However, due to the marked similarities between head and neck cancers and lung cancers in this regard, these tests are usually inconclusive. "In order to solve this problem, we tested tissue samples for a specific chemical alteration known as DNA methylation," explains Prof. Capper who, like Prof. Klauschen, is a Scientific Member of the DKTK in Berlin. He adds: "We know from earlier studies that DNA methylation patterns in cancer cells are highly dependent on the organ in which the cancer originated."

Working with Prof. Dr. Klaus-Robert Müller, Professor for Machine Learning at TU Berlin, the research group employed artificial intelligence-based methods to render this information useful in practice. The researchers used DNA methylation data from several hundred head and neck and lung cancers in order to train a deep neural network to distinguish between the two types of cancer. "Our neural network is now able to distinguish between lung cancers and head and neck cancer metastases in the majority of cases, achieving an accuracy of over 99 percent," emphasizes Prof. Klauschen. He continues: "To ensure that patients with head and neck cancers and additional lung cancers will benefit from the results of our study as quickly as possible, we are currently in the process of testing the implementation of this diagnostic method in routine practice. This will include a prospective validation study to ensure that the new method can be made available to all affected patients."

Having worked alongside the researchers from Charité, the Director of the Berlin Center for Machine Learning (BZML), Prof. Müller, is similarly delighted at their results: "Artificial intelligence is playing an increasingly important role, not only in our daily lives and in industry, but also in natural sciences and medical research. The use of artificial intelligence is, however, particularly complex within the medical field; this is why, until now, research findings have only rarely delivered direct benefits for patients. This could now be about to change."

Cancer patients who miss an urgent referral appointment for their symptoms are 12% more likely to die within 12 months of diagnosis, a major new study has found.

The study, funded by Yorkshire Cancer Research, showed that male patients and those under 30 or over 85 years of age are more likely to skip their appointment, as are people who live in disadvantaged neighbourhoods and people who have been referred due to gastrointestinal problems.

The authors of the study say that more support is needed for patients at risk of non-attendance.

Led by researchers at the University of York and Hull York Medical School, the study looked at data from more than 100,000 patients who had been urgently referred by around 100 different GP practices in the North of England.

The majority of patients in the study (95%) attended their referral appointment, but a significant minority (5% or 5,673 people) did not.

While the study found that only one in 18 of the patients who skipped their appointment went on to be diagnosed with cancer - compared to one in 10 of those who did attend - the outlook for patients who missed their appointment and did have cancer was significantly worse.

The study revealed that 34.6% of non-attending patients with cancer had an advanced stage of the disease at diagnosis compared to 18.4% of attenders with cancer.

Having a more advanced stage of the disease is likely to be a reason why more non-attending patients with cancer died within a year of diagnosis (31.3% compared to 19.2% of attenders), the researchers say.

Dr Peter Knapp, from the Department of Health Sciences at the University of York and Hull York Medical School, said: "Our study showed cancer diagnosis was less likely in non-attending patients but those who are diagnosed have worse outcomes than attending patients with cancer. This may be due to later presentation to their GP and more advanced disease at referral.

"Non-attendance at urgent referral appointments for suspected cancer involves a minority of patients, but happens in somewhat predictable groups. For example, we found that patients with suspected gastrointestinal cancer were among the least likely to attend - this may be due to concerns about unpleasant or embarrassing procedures.

"Our research suggests that more could be done to identify individuals at risk of non-attendance and offer extra support."

The NHS's 'Two Week Wait' policy aims to ensure that patients with suspected cancer are seen by a consultant within two weeks of an urgent GP referral.

While there is more awareness around the issues of ignored cancer screening invitations and the waste of resources incurred from missed GP appointments, the study is the first to focus on non-attendance of symptomatic patients referred due to suspected cancer.

Dr Stuart Griffiths, Director of Research and Services at Yorkshire Cancer Research, said: "Early diagnosis is vital in ensuring more people survive cancer, but there are many challenges facing both doctors and patients when it comes to accessing diagnosis and treatment swiftly. The charity is looking at ways it can work with the NHS and other research partners to determine how it can address factors leading to non-attendance at urgent referral appointments."

A research group led by Professor Tomoyuki Furuyashiki and Associate Professor Shiho Kitaoka (Graduate School of Medicine) in collaboration with researcher Yasuhisa Ano of Kirin Holdings have made discoveries regarding the effect of the dipeptide Leucine-Histidine (LH) in suppressing microglial activation and depression-associated emotional disturbances. LH dipeptide is found in fermented foods such as blue cheese and natto (fermented soy beans). Foods rich in LH dipeptide may be a safe, preventive method for maintaining good mental health.

These research results were first reported in the online academic journal 'Nutrients' on September 9 2019.

Introduction:

Depression is one of the most common mental disorders and remains difficult to treat, as numerous patients don't respond to available psychological or pharmacological treatments. Consequently, possible methods of preventing depression in daily life, such as nutritional approaches, are gaining increasing attention.

Recent studies have shown the role of microglia in depression. Microglia are immune cells in the central nervous system that are normally responsible for removing waste products. However, they can cause inflammation in the brain when they are activated. Many findings have suggested a link between depression and brain inflammation, and anti-inflammatory drugs have been shown to improve depression symptoms in trials. It has also been reported that consumption of fermented products is associated with reduced depression symptoms. However, the nutritional components that suppress microglia activation and depression are not well understood.

Results:

In this study, the effects of 336 dipeptides on microglia activation were evaluated, and LH dipeptide was discovered to be a potent anti-inflammatory agent. LH dipeptide inhibited the secretion of inflammatory cytokines (signaling molecules such as TNF-α that are secreted from cells to promote inflammation) from microglia. Further studies were performed on mice to evaluate LH dipeptide's impact on brain inflammation and emotional disturbances.

The LH dipeptide was labeled with radioactive isotopes so that its movement through the body could be tracked; this confirmed that the dipeptide travelled to the brain after oral administration. To analyze the effect of LH dipeptide on brain inflammation, mice were injected with LPS (a bacterial component that elicits inflammation), which increased the amount of the cytokines TNF-α and IL-1β in the frontal cortex and hippocampus of the brain. Repeated oral administrations with LH dipeptide reduced the amounts of these cytokines in the brain. These results show that LH dipeptide suppressed brain inflammation (Figure 1).

They then analyzed the effect of LH dipeptide on depression-associated emotional disturbances. First, individual mice were exposed to the Tail Suspension Test (TST), where they were suspended by their tails in a box for 6 minutes. The time that mice are immobile was measured, as this is a behavioral indication of depression. LPS treatment induced brain inflammation and prolonged immobility time in the TST. However, repeated oral administration with LH dipeptide was shown to prevent this pro-depressive effect of LPS.

Second, mice were confronted with repeated social defeat stress (R-SDS). This involved putting each of the test mice in cages with an aggressive mouse for 10 minutes daily over a period of several days. Defeated mice that were treated with LH dipeptide showed less social avoidance after the R-SDS. These mice also displayed less anxiety during the Elevated Plus Maze test, as they spent more time in the open arms of the maze*. These results suggest that oral administration of LH dipeptide prevents depression-associated emotional disturbances.

Conclusions and further study:

Overall, the findings of this research show that repeated oral administrations of LH dipeptide suppress microglia activation and reduce depression-associated emotional disturbances in mice. It is hoped that these results can be replicated in humans. The researchers propose that consuming foods rich in LH dipeptide may be a safe, preventative method for maintaining good mental health.

DALLAS, Sept. 12, 2019 -- The emerging practice of precision medicine could one day personalize heart failure care by identifying groups of patients more likely to develop heart failure and tailoring which medications and other therapies could be most effective for them, according to a new scientific statement from the American Heart Association, published in the journal Circulation: Genomic and Precision Medicine.

Precision medicine uses information about a person's genetic make-up, metabolism and other biological and environmental factors to determine what strategies can better prevent or treat a health condition. The goal is to provide personalized treatment that is more likely to be successful for each individual patient, rather than a one-size-fits-all approach.

This new American Heart Association statement provides a state-of-the-science overview of heart failure as it relates to the different aspects of precision medicine, including how variations in genes, biomarkers in the blood or bacteria in the gut can predict the risk of heart failure and how a person may respond to various treatments.

"We aim to improve care for everyone with heart failure by more clearly defining the best treatment options for specific groups of people," said Sharon Cresci, M.D., chair of the statement writing group and associate professor of medicine and genetics at Washington University in St. Louis, Missouri. "This statement details the potential of precision medicine to improve patient outcomes."

The prognosis for people with heart failure has improved in recent decades as research studies have demonstrated the effectiveness of various medications. However, within those clinical trial populations are groups of people who are less likely to benefit from the drug and some who may have serious side effects.

"Major clinical trials often treat large numbers of patients with one medication, and if there is a positive result, the use of that medication is likely to be incorporated into guidelines for treatment," Cresci said. "Yet, within the large group of clinical trial participants, there are often some with no response and some with an adverse response. Precision medicine approaches can help us identify who those non-responders or adverse responders are likely to be so we can find different treatment options for them."

To do this, it is important that clinical trials enroll a diverse group of participants, according to Cresci.

"Historically, clinical trial participants have been predominantly white people with particular genetic variants. People with different racial and ethnic ancestry have different genetic variants, therefore, they may not have the same response to a medication or other treatment," she said. "Researchers conducting clinical trials recognize this issue and are trying to increase diversity among clinical trial participants so we can find the optimal treatment approaches for each population group."

Some aspects of precision medicine are already routinely used by healthcare providers treating heart failure. For example, the blood level of a biomarker called B-type natriuretic peptide is a sensitive indicator of whether heart failure is worsening or if treatments are helping. It can also help determine whether symptoms such as shortness of breath are due to heart failure rather than another medical problem.

"The use of biomarkers is probably the most advanced aspect of precision medicine currently used in the treatment of heart failure. Most others are still in their infancy, and we hope in the future to combine multiple aspects of precision medicine to improve patient care and outcomes," Cresci said.

Because health professionals may be unfamiliar with one or more precision medicine approaches, the statement aims to be an educational resource by combining information on how each applies to heart failure.

"This statement also outlines how advances in technology have and can be used to precisely define variability within population groups, and how these advances can be applied to specific patients with heart failure," said Naveen L. Pereira, M.D., vice-chair of the scientific statement writing committee and professor of medicine and associate professor of pharmacology at the Mayo Clinic College of Medicine in Rochester, Minnesota. "A composite of results from these various precision medicine techniques may also allow us to identify previously undiscovered biology that could lead to the discovery of new medications and treatments for people with heart failure."

Recognizing the value of this multi-faceted and personalized approach to heart disease, the American Heart Association established the Institute for Precision Cardiovascular Medicine in 2015. It provides:

Training in new skills that medical researchers will need, such as data science and artificial intelligence;

A cloud-based platform for scientists to collaborate and share data internationally;

An initiative to involve women across the United States in health research; and

A drug discovery center to use the power of supercomputing to rapidly predict the outcomes of possible new treatments.

"The field of precision medicine is still in its infancy, with infrastructure and programs to be built. We'll need specialized training for clinicians, processes for sharing information across large databases and guarantees for patient privacy," Cresci said. "It's exciting to realize the potential life-saving innovations on the horizon through precision medicine."

Cancer survival in the UK has improved since 1995, although it still lags behind other high-income countries, according to new analysis* by the International Cancer Benchmarking Partnership (ICBP), which is managed by Cancer Research UK.

The study, published in Lancet Oncology, looked at 3.9 million cancer cases between 1995 and 2014, in seven comparable countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK).

This is the first international study to look at changes in cancer survival alongside incidence and mortality for cancers of the oesophagus, stomach, colon, rectum, pancreas, lung and ovary. Exploring these three key measures allows us to better understand how countries like the UK compare in the prevention, diagnosis and treatment of different cancers.

Encouragingly, one-year and five-year survival has improved across all seven cancer sites in the UK across the 20-year period. Five-year survival for rectal cancer in the UK rose by 14 percentage points** since 1995, from 48% to 62%. The UK also has one of the highest increases in five-year survival - almost 12 percentage points - across all countries for colon cancer. This can potentially be attributed to advances in treatment such as better surgery, among other factors.

Additionally, one-year survival for lung, ovarian and oesophageal cancer all increased by around 15 percentage points in the last 20 years. Though great progress has been made, the UK remains near the bottom of the rankings, and has not yet caught up with the other countries.

Cancer Research UK's clinical adviser, John Butler, who co-authored the study and is a consultant surgeon at the Royal Marsden, said: "There isn't one specific reason why survival in the UK has improved - it's a combination of many different factors. Over the last twenty years we've seen improvements in cancer planning, development of national cancer strategies and the rollout of new diagnostic and treatment services.

"For lung, ovarian, and oesophageal cancer in particular, survival has increased largely because the quality of surgery has radically improved, and more surgery is taking place than before. More people are being looked after by specialist teams, rather than surgeons who aren't experts in that area. But while we're still researching what can be done to close the survival gap between countries, we know continued investment in early diagnosis and cancer care plays a big part. Despite our changes we've made slower progress than others."

Sara Hiom, Cancer Research UK's director of early diagnosis, said: "More people than ever before are surviving cancer thanks to research and targeted improvements in care. But, while we're on the right track, the numbers show we can certainly do better.

"We will not see the necessary improvements in diagnosis and access to treatment unless we have enough of the right staff across our NHS. Cancer Research UK has been calling for staff shortages to be addressed because, quite simply, it will give people a better chance of surviving their cancer. If we are to achieve world class cancer outcomes in the UK, then we need to see comparable investment in the NHS and the systems and innovations that support it. It's never been a more crucial time for the Government to put new money where it matters."

Gorillas are social animals, living in groups that females will migrate to join, becoming members of harems. Though some factors motivating these migrations were previously known, a research team affiliated with the CNRS and Université de Rennes 1 has just demonstrated that female gorillas are able to avoid conspecifics liable to transmit yaws, which leads to conspicuous ulcers on the animals' faces. While studying 593 gorillas for over a decade, the scientists observed that females leave males and overly diseased groups to join healthier ones, avoiding other sick groups at all costs. The team's findings, which are published in Ecology's September issue, suggest gorillas learn the disease is contagious and are able to detect one of its symptoms in others, namely disfigurement.